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The long noncoding RNA LUCAT1 promotes tumorigenesis by controlling ubiquitination and stability of DNA methyltransferase 1 in esophageal squamous cell carcinoma

 Jung-Ho Yoon  ;  Bo-Hyun You  ;  Chan Hyuk Park  ;  Yeong Jin Kim  ;  Jin-Wu Nam  ;  Sang Kil Lee 
 Cancer Letters, Vol.417 : 47-57, 2018 
Journal Title
 Cancer Letters 
Issue Date
DNA methylation ; DNA methyltransferase 1 ; Epigenetics ; Esophagus squamous cell carcinoma ; LUCAT1 ; Long-noncoding RNA
Available targeted therapies for esophageal squamous cell carcinoma (ESCC) are limited; thus, further genetic and epigenetic studies are needed. Recently, many long noncoding RNAs (lncRNAs) have been reported to be involved in various cancers. Here, we investigated whether the lncRNA LUCAT1 was related to the carcinogenesis of ESCC based on previous studies in lung cancer. LUCAT1 was significantly upregulated in ESCC cell lines and cancer tissue compared with normal cells and adjacent normal tissues. LUCAT1 knockdown reduced cell proliferation, induced apoptosis, and upregulated tumor-suppressor genes by reducing DNA methylation in KYSE-30cells. Moreover, LUCAT1 siRNA reduced DNA methyltransferase 1 (DNMT1) protein levels without affecting transcription. Patients with high LUCAT1 expression had significantly lower survival rates than patients with low LUCAT1 expression. Our results thus suggest that LUCAT1 regulates the stability of DNMT1 and inhibits the expression of tumor suppressors through DNA methylation, leading to the formation and metastasis of ESCC. We identified LUCAT1 as a potential target for drug development and as a biomarker for ESCC.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Young Jin(김영진)
Lee, Sang Kil(이상길) ORCID logo https://orcid.org/0000-0002-0721-0364
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